Project Summary: Plasmodium falciparum malaria is a major health problem for pregnant women since it increases maternal mortality and poor pregnancy outcomes. In addition, infants whose mothers have malaria during pregnancy are at an increased risk of developing severe malaria, anemia, asthma and dying during the first year of life than those whose mothers remain malaria-free. Our long-term goal is to improve the health of women and children living in sub-Saharan Africa. Accordingly, scientists at the University of Yaounde, Cameroon and University of Hawaii propose to answer key questions about the current recommended strategy for prevention of malaria during pregnancy, namely intermittent preventive treatment using sulfadoxine-pyrimethamine (IPT-SP). Specifically, we seek to determine if IPT-SP administered during the 2nd and/or 3rd trimester influences 1) the acquisition of antibodies (Ab) that inhibit parasite sequestration in the placenta, 2) placental pathology associated with low birthweight babies, 3) transplacental transfer of antimalarial IgG to vaccine-candidate antigens, 4) in utero priming of fetal T and B cells, and 5) the number and severity of P. falciparum infections infants have, as well as their rate of acquisition of immunity, during the first year of life. Studies will be conducted in the city of Yaounde where transmission is ~1 infectious bite per month and in rural villages where individuals receive ~0.7 infectious bites per night. The proposed studies will be the first to evaluate IPT-SP in pregnant women living in Central/West Africa and in an area where transmission of malaria is low. It will also be the first to study the effect of IPT-SP on production of Ab to the malaria antigen VAR2csa and how this relates to placental pathology associated with LEW babies. Finally, the study will be the first to determine if IPT-SP reduces the level of protective immunity infants have at birth and how this influences malaria episodes and Ab responses in infants during the 1st year of life. Relevance: The proposed study will help determine the strengths and weaknesses of the method currently recommended by the World Health Organization for prevention of malaria in pregnant women living in developing countries. New information from this study should lead to improved health care for African mothers and their children.